a study of prt2527 in participants with advanced solid tumors

Conditions: Sarcoma; Castrate Resistant Prostate Cancer; Hormone Receptor Positive HER2 Negative Breast Cancer; Non-small Cell Lung Cancer; Solid Tumors With Known MYC Amplification

Summary: this is a phase 1 dose-escalation and confirmation study of prt2527, a cyclin-dependent kinase 9 (cdk9) inhibitor, in participants with advanced solid tumors. the purpose of this study is to define the dosing schedule, and maximally tolerated dose to be used in subsequent development of prt2527.

this is a multicenter, open-label, dose-escalation and confirmation phase 1 study of prt2527, a cdk9 inhibitor, evaluating participants with selected advanced/metastatic sarcomas displaying a documented gene fusion, castrate resistant prostate cancer, hormone receptor positive her2-negative breast cancer, advanced/metastatic non-small cell lung cancer, and solid tumors displaying myc amplification. the study plan expects to evaluate approximately six dose levels of approximately 1-6 participants per dose level; however additional and/or intermediate dose levels may be explored. taking into account pharmacokinetic and pharmacodynamic data from the preceding dose levels, the dose may be escalated until a dose limiting toxicity is identified. the total sample size will be approximately 30 patients for mtd and rp2d determination.

Eligibility criteria:
inclusion criteria: * tumor types under study 1. selected sarcomas with a documented gene fusion 2. castrate resistant prostate cancer (crpc) 3. hormone receptor positive (hr+), her2 negative (her2-) breast cancer 4. non-small cell lung cancer (nsclc) 5. myc amplified solid tumors * must have measurable disease per recist 1.1; participants with crpc or sarcoma may have nonmeasurable but evaluable disease * eastern cooperative oncology group (ecog) performance score of 0 or 1 * adequate organ function * must provide tumor tissue sample to the central laboratory for biomarker analysis * participants must have recovered from the effects of prior cancer-related therapy, radiotherapy, or surgery to ≤ grade 1 exclusion criteria: * primary malignancies of the cns, or uncontrolled cns metastases, including impending spinal cord compression * have a corrected qt interval \>480 msec from prior or baseline * have impaired cardiac function or clinically significant cardiac disease * treatment with strong inhibitors or inducers of cyp3a4 * prior exposure to a cdk9 inhibitor * history of another malignancy except for: 1. curatively treated malignancy with no known active disease 2. curatively treated non-melanoma skin cancer without evidence of disease 3. curatively treated carcinoma in situ without evidence of disease * have undergone major surgery within 2 weeks prior to week 1 day 1 * have had chemotherapy, biologic therapy, targeted therapy, immunotherapy, extended-field radiotherapy, or investigational agents within 5 half-lives or 28 days (whichever is shorter) prior to administration of the first dose of study drug on week 1 day 1.

Keywords: breast cancer castrate resistant prostate cancer cdk9 inhibitor crpc cyclin-dependent kinase 9 hormone receptor positive her2 negative breast cancer hr+/her2- breast cancer non-small cell lung cancer nsclc prostate cancer prt2527 refractory solid tumors relapsed solid tumors sarcoma